4-cyanoformyl-1-alkyl pyridinium halide oxime and its derivatives

ABSTRACT

1. Compounds having the formula WHERE R is an alkyl group of 1 to 4 carbon atoms and X is selected from the group consisting of C1 , Br and I .

nited States Patent Robert H. Poirler Columbus, Ohio;

Bernard W. Fromm, Edgewood; Edward J. Poziomek, Edgewood; John A. Stein, Parkville; David N. Kramer, Stevenson, Md.

Sept. 11, 1962 Nov. 30, 197 l The United States of America as represented by the Secretary of the Army 72] Inventors [21 Appl. No. [22] Filed [45] Patented [73] Assignee 252/408 [51] lnt.Cl ..C07d 31/46 [50] FieldofSearch 260/2949 Primary Examiner-Leland A. Sebastian An0meysGe0rge Renehan and Edward J. Kelly CLAIM q aqahevin the emales GEN where R is an alkyl group of l to 4 carbon atoms and X is selected from the group consisting ofC l Br" and i.

4-CYANOFORMYL-l-ALKYL PYRIDINIUMHALIDE OXIME AND ITS DERIVATIVES The invention described herein may be manufactured and used by or for the Government of the United States of America for governmental purposes without the payment to us of any royalty thereon.

This invention is directed to new chemical compounds which are useful as colorimetric detectors for phosphorus cholinesterase inhibitors.

Various oximes have been used in the past to detect the agents as is shown by US Pat. Nos. 2,865,719; 2,867,509; 2,926,072; and 2,929,719. We have discovered a new series of compounds which will react with phosphorus compounds of the type disclosed in US. Pat. No. 3,014,943 and British Pat. No. 797,603 to give an almost instantaneous color change from orange, yellow to blue followed by a red fluorescent color under ultraviolet light.

These compounds have the general formula:

GEN

Swhere R is a lower alkyl group and X is a chlorine, bromine, or iodine radical, and the general formula:

Swhere R is the same as above.

The compound of the first formula can be prepared from 4- picolyl chloride (a-chloro-4-picoline) by adding it to sodium cyanide in an alcohol to obtain 4-pyridyl acetonitrile. This is followed by an isonitrosation reaction with alkyl nitrile to obtain a-isonitroso-4-pyridylacetonitrile. When this product is quaternized with an alkyl halide in an alcohol, the compounds are obtained.

We have further found that compounds of the first formula can be reacted with an excess amount of bases such as potassium xanthogenate, sodium ethoxide, sodium methoxide, sodium hydroxide and concentrated ammonium hydroxide, to produce compounds of the second group.

It was also found that whereas compounds of the first group detect only compounds of the type disclosed in the above United States and British patents, with the addition of a strong base such as potassium xanthogenate the selectivityof these compounds were expanded to detect one of the "G agents, i.e., ethyl dimethylphosphoramide cyanidate or GA. All these compounds are stable compounds (especially to lights) that can be used in paints, powders, crayons and spray detector formulations in a manner well known in the art.

EXAMPLE l A slurry of 60 g. of sodium cyanide in 60 ml. of water and 300 ml. of ethyl alcohol was prepared at room temperature. 4- picolyl chloride hydrochloride was added to this slurr-y portionwise until a total of 49.2 g. were added. After the mixture was stirred at room temperature overnight, the salts were removed by filtration, and the filtrate was concentrated under reduced pressure. The concentrate was poured into ice water, and the mixture was extracted with portions of chloroform totaling nearly 500 ml. The chloroform layer was washed with water to remove most of the intensely colored impurity, dried over anhydrous sodium sulfate and distilled under reduced pressure. In this manner 11.0 g. of 4-pyridylacetonitrile was collected as a colorless oil that solidified in the receiver, with a freezing point of 425 C. The product slowly acquired a pinkish color upon standing at room temperature.

To an ice cold solution of 19.5 g. of n-butyl nitrite in 150 ml. of ethanol to which 4.35 g. of metallic sodium had been added, 15.2 g. of 4-pyridylacetonitrile in 30 ml. ofethanol was added dropwise. The sodium salt of the isonitrosated product soon began to separate as a yellow powdery solid. After the reaction mixture had been stirred in the cold for 2 hours, the

' solid was removed by filtration, rinsed with ethanol and dried in a vacuum oven. The yield ofsalt was 15.3 g. By evaporating the filtrate to dryness, redissolving the residue in water and acidifying the solution with acetic acid, there separated 9.4 g. of free a-isonitroso-4-pyridylacetonitrile as a pinkish white colored solid. The pink colored impurity was readily removed by treatment with activated charcoal of a warm ethanolic solution of the crude product. Nearly pure white needles of aisonitroso-4-pyridylacetonitrile, m.p. 278-279 C. then separated upon cooling the ethanol solution.

, A slurry of 14.0 g. of a-isonitroso-4-pyridylacetonitrile in 150 ml. of methanol containing 50 ml. of methyl iodide was refluxed for 32 hours whereupon the isonitroso compound slowly dissolved forming a reddish solution. The methanol and excess methyl iodide were evaporated, thus leaving 29.6 g. of reddish-orange solid. Recrystallization of the crude product from a mixture of 50 ml. of ethanol and 150 ml. of benzene yielded 23.25 g. of 4-cyanoformyl-l-methyl-pyridinium iodide oxime. The product consists of yellowish-orange needles m.p. l72-l73 C. (dec.). Recrystallization from an ethyl alcohol benzene mixture raised the melting point to l80.5"-l8l C. (dec.). However, the crystals retained approximately one-half mole of benzene even after drying at 50 C.

Calculated for C H I N;, 0.%C,, H C,40.25; H.336; 1.38.7 Found: C,39.6; 11,3.5; 1.39.6

EXAMPLE 11 line dusty rose precipitate of m.p. 263-265 (dec.

Calculated for C H, N, 0: C, 59.6; H,4.4; N,26.l Found: C,59.9; l-l,4.5; N,25.7

EXAMPLE 111 To a mixture of 3.0 g. (0.019 mole) of 4-cyanoformyl-1- methyl-pyridinium oximate in 50 ml. of methanol was added an equimolar amount of aqueous hydrogen chloride. The compound went into solution immediately. Ether was then added to give a yellow oil. The oil was dissolved in methanol.

Upon the addition of ether to the methanol solution, a pale yellow solid precipitated out. After purification of this solid by refluxing a methanol solution of it with activated charcoal and reprecipitation with ether, 1.3 g. of 4-cyanoformyl-l-methylpyridinium chloride oxime, a colorless solid m.p. 229-233 C. (dec) was obtained.

Calculated for C H N 0 CH6 H O C,47.5; H,4.2; N,20.7

Found: C,47.8; H, 4.0; N,20.6

EXAMPLE IV To a mixture of 1.9 g. (0.012 mole) of 4-cyanoformyl-lmethyl-pyridinium oximate in 50 ml. of methanol was added fuming hydrogen bromide dropwise until a complete solution was effected. Subsequently, 1.35 g. of the product, 4- cyanoformyl-l-methyl-pyridinium bromide oxime, a colorless solid, m.p. 247-252 C., was isolated and purified in a manner similar to the method described in example 111.

Calculated for C H, Br N 0: C,29.6; H,3.3; Br 33.3

Found: C,40. l; H,3.4; Br,32.9

In the foregoing examples, only the use of methyl halides have been illustrated. It is to be understood that this invention also contemplates the use of ethyl, n-propyl and n-butyl halides.

The compounds of group I] are interesting in that they ap- 1 (EN parently resonate between the following forms:

' )C can 5 R- =N Swhere R is an alkyl group of one to four carbon atoms and X is selected from the group consisting ofCl, Br and l.

2. Compounds having the formula R-- N -c =N- 0- This is confirmed by ultraviolet absorption spectra and by analogy to other zwitter-ion type compounds. The pyridinium oximate structure is the major contributor to the ground state structure of the molecule. Additionally, ultraviolet and visible absorptiomspectra in various organic solvents show that intramolecular charge-transfer complexes exist in this class of I compounds 5. 4-cyanoformyl-7-methyl-pyridimum chloride oxime.

w l i 6. 4-cyanoformyll -methyl-pyridinium bromide oxime. 1. Compounds having the formula 4- n! w m Swhere R is an alkyl group ofone to four carbon atoms. 3. 4-cyanoformyl-l-methyl-pyridinium iodide oxime. 4. 4-cyanoformyll -methyl-pyridinium oximate. 

1. COMPOUNDS HAVING THE FORMULA
 2. Compounds having the formula
 3. 4-cyanoformyl-1-methyl-pyridinium iodide oxime.
 4. 4-cyanoformyl-1-methyl-pyridinium oximate.
 5. 4-cyanoformyl-1-methyl-pyridinium chloride oxime.
 6. 4-cyanoformyl-1-methyl-pyridinium bromide oxime. 